Variant chrX-129471289-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001282874.2(SMARCA1):c.2480C>G(p.Ala827Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 1,196,932 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000030 ( 0 hom. 12 hem. )

Consequence

SMARCA1
NM_001282874.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

Variant links:

Genes affected

SMARCA1 (HGNC:11097): (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 1) This gene encodes a member of the SWI/SNF family of proteins. The encoded protein is an ATPase which is expressed in diverse tissues and contributes to the chromatin remodeling complex that is involved in transcription. The protein may also play a role in DNA damage, growth inhibition and apoptosis of cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

SMARCA1 links:

SMARCA1 (HGNC:):

SMARCA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19315219).

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMARCA1	NM_001282874.2 linkuse as main transcript	c.2480C>G	p.Ala827Gly	missense_variant	20/25	ENST00000371121.5	NP_001269803.1	B7ZLQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMARCA1	ENST00000371121.5 linkuse as main transcript	c.2480C>G	p.Ala827Gly	missense_variant	20/25	1	NM_001282874.2	ENSP00000360162.4	B7ZLQ5
SMARCA1	ENST00000371123.5 linkuse as main transcript	c.2444C>G	p.Ala815Gly	missense_variant	19/24	1		ENSP00000360164.2	A0A0A0MRP6
SMARCA1	ENST00000371122.8 linkuse as main transcript	c.2480C>G	p.Ala827Gly	missense_variant	20/25	1		ENSP00000360163.4	P28370-1
SMARCA1	ENST00000617310.4 linkuse as main transcript	n.2798C>G		non_coding_transcript_exon_variant	18/23	2

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111957

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34133

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000111

AC:

AN:

179980

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

64688

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1084975

Hom.:

Cov.:

AF XY:

0.0000342

AC XY:

AN XY:

351209

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000397

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111957

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34133

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000166

EpiControl

AF:

0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2024

The c.2480C>G (p.A827G) alteration is located in exon 20 (coding exon 20) of the SMARCA1 gene. This alteration results from a C to G substitution at nucleotide position 2480, causing the alanine (A) at amino acid position 827 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

T;T;.

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.057

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Benign

1.6

L;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.23

Sift

Benign

0.19

T;T;.

Sift4G

Benign

0.34

T;T;T

Polyphen

0.17

B;.;B

Vest4

0.11

MVP

0.73

MPC

0.84

ClinPred

0.21

GERP RS

5.5

Varity_R

0.21

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over